(1) Field of the Invention
This invention relates to a method and medical agents for the photodynamic diagnosis and photodynamic therapy of the arthritis, especially the arthritis of mammals. More particularly, the medical agents used in the present invention belong to specific fluorescent compounds having a tetrapyrrole skeletal structure. When an effective quantity of the medical agent is administered to an animal patient, the agent is accumulated in the affected part of the body.
When light rays of necessary wavelength are applied to an affected joint to be diagnosed or treated, the agent generates fluorescence in the affected portion, thereby enabling the detection of arthritis. This is called as photodynamic diagnosis. In the therapeutic treatment, when light rays of appropriate wavelength and intensity are applied to a lesion, the agent is excited to produce a cytotoxic effect and the affected cells in arthritic lesion are necrosed. This is called as photodynamic therapy. The present invention relates to the diagnosis and the therapy of this kind applied to arthritis, especially rheumatoid arthritis.
(2) Description of the Prior Art
Rheumatoid arthritis is a chronic systemic disease mainly causing to occur polyarthritis as a cardinal symptom. This disease is initiated by the pain and swelling in small joints of hands and feet, or in elbow joints and knee joints, and other joints in whole body are then affected little by little. In the initial phase of the disease, the hyperplasia of the synovia of the affected joint begins by some stimulation of the unknown antigen, and the synovial hyperplasia is maintained and prolonged by the monokine cascade system to be a tumor-like condition. The constituents of the joint such as cartilage or ligament or bone are destroyed by the enzymes produced by these synovia and followed by the destruction of the joints.
This pathological condition is observed in all human races and distributed all over the world.
In the diagnosis of the rheumatoid arthritis, it is necessary to identify the outbreak of rheumatoid factor and the existence of inflammatory response by means of blood test, the occurrence of swelling and pain in joints, and further the existence of distortion of bones by means of X-ray inspection. In view of the results of these inspections, the diagnosis of rheumatoid arthritis can be attained.
Since any satisfactory etiologic therapy for the rheumatoid arthritis has not been developed, the nosotropic treatment to preserve affected lesions is employed according to respective cases. However, the efficacy of such treatments is no yet clarified at present. That is, in the first place, medication is done in order to promote the remission of disease by administering a non-steroidal antiphlogistic lenitive, at the same time, the physiotherapy is adopted. In spite of the medication, if the swelling takes a bad turn and the hyperplasia of synovial membrane become noticeable, synovectomy is carried out by arthrotomy or by arthroscopic method. The total arthroplasty is employed in order to restore the function of the joint by substituting the artificial prosthesis for the destructed joint.
In order to prevent the destruction of the joint constituents, the cellular immunologic responses in the synovia must be reduced throughout the disease process, especially in the early stage.
There is hitherto known a method of diagnosis and therapy of rheumatoid arthritis by administering a hematoporphyrin derivative to rats which suffer from adjuvant induced arthritis and applying light rays to the rats. For instance, "Rheumatoid Arthritis and Laser (Effect of laser irradiation to adjuvant induced arthritis)", The RYUMACHI (Official Journal of the Japan Rheumatism Association), Vol. 23, pp 574-575, 1983.
However, it was clarified through the experiments carried out by the present inventors that, when a typical hematoporphyrin derivative, Photofrin II, is used, it cannot be taken selectively into a rheumatoid arthritic lesion and a noticeable therapeutic effect to the rheumatoid arthritis cannot be expected.
Incidentally, the compounds themselves used in the present invention are already known as diagnostic and therapeutic medicines for cancer. However, the inventors have never known any instance concerning the use of the relevant compounds for the diagnosis and treatment of arthritis. The field of art according to the present invention is, of course, different from the field of art in the diagnosis and the therapy of cancer.
Furthermore, the inventors are acquainted with the following literatures, however, the object of the studies are different from that of the present invention.
(a) "Systemic Immunosuppression Induced by Photodynamic Therapy (PDT) is Adoptively Transferred by Macrophages", PHOTOCHEMISTRY AND PHOTOBIOLOGY, Vol. 49, pp 453-458, 1989.
(b) "Immunological Suppression in Mice Treated with Hematoporphyrin Derivative Photoradiation", CANCER RESEARCH, Vol. 46, pp 1608-1611, 1986.